ABSTRACT
The Disease Control Priorities Project (DCPP), a joint project of the Fogarty International Center of the US National Institutes of Health, the WHO, and The World Bank, was launched in 2001 to identify policy changes and intervention strategies for the health problems of low-income and middle-income countries. Nearly 500 experts worldwide compiled and reviewed the scientific research on a broad range of diseases and conditions, the results of which are published this week. A major product of DCPP, Disease Control Priorities in Developing Countries, 2nd edition (DCP2), focuses on the assessment of the cost-effectiveness of health-improving strategies (or interventions) for the conditions responsible for the greatest burden of disease. DCP2 also examines crosscutting issues crucial to the delivery of quality health services, including the organisation, financial support, and capacity of health systems. Here, we summarise the key messages of the project.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Global Health , Health Priorities , Preventive Health Services/organization & administration , Public Health/statistics & numerical data , Acquired Immunodeficiency Syndrome/economics , Acquired Immunodeficiency Syndrome/prevention & control , Adult , Child , Cost-Benefit Analysis , Humans , Preventive Health Services/economics , Preventive Health Services/trends , Public Health/economicsABSTRACT
Hirano bodies are eosinophilic, actin-rich inclusions found in autopsied brains in numerous neurodegenerative diseases. The mechanism of Hirano body formation is unknown. Mass spectrometry analysis was performed to identify proteins from partially purified model Hirano bodies from Dictyostelium This analysis identified proteins primarily belonging to ribosomes, proteasomes, mitochondria and cytoskeleton. Profilin, Arp/2/3 and WASH identified by mass spectrometry were found to colocalise with model Hirano bodies. Due to their roles in actin regulation, we selected these proteins for further investigation. Inhibition of the Arp2/3 complex by CK666 prevented formation of model Hirano bodies. Since Arp2/3 activation occurs via the WASH or WAVE complex, we next investigated how these proteins affect Hirano body formation. Whereas model Hirano bodies could form in WASH-deficient cells, they failed to form in cells lacking HSPC300, a member of the WAVE complex. We identified other proteins required for Hirano body formation that include profilin and VASP, an actin nucleation factor. In the case of VASP, both its G- and F-actin binding domains were required for model Hirano body formation. Collectively, our results indicate that de novo actin polymerization is required to form model Hirano bodies.